Kinetics of serological responses in influenza A(H7N9)-infected patients correlate with clinical outcome in China, 2013.

The novel avian influenza A(H7N9) infection has recently emerged to cause severe respiratory illness in China. The objectives of this study were to define the kinetics of the antibody responses in patients with influenza A(H7N9) disease and to correlate these kinetics with clinical outcome. Serial serum samples were obtained at intervals of three to four days from 18 patients with virologically confirmed A(H7N9) disease in Shanghai. We determined the kinetics of the haemagglutination inhibition (HI) and A(H7H9) pseudotype neutralisation antibody (Nab) responses and correlated these with clinical outcomes. Most patients had robust serological responses by both HI and Nab tests. Taking into account censoring due to time of testing and death, the median time from onset of illness to Nab titre ≥1:40 was 14 days (95% confidence interval (CI): 11­18 days) in the fatal cases and 10.5 days (95% CI: 7­12) in the survivors (p=0.003). The two groups did not differ in initial Nab titres, but the rate of increase in Nab titres was significantly faster for survivors by approximately 10-fold per 15 days (p=0.007). Early and rapid induction of Nab was correlated significantly with better clinical outcome.

Diffuse and concentrated nitrogen sewage pollution in island environments with differing treatment systems.

Macroalgae is an under-utilised tool as a bioindicator of anthropogenic nitrogen loading to the coastal environment in the UK. This study compared two island systems-Jersey (Channel Islands) and St Mary's (Isles of Scilly) to assess how differing sewerage infrastructure affects nitrogen loading. A total of 831 macroalgae samples of Fucus vesiculosus and Ulva sp. were analysed for nitrogen isotopes (δ15N). Elevated δ15N values were recorded for Jersey (> 9‰) in St Aubin's Bay-caused by the outflow of the Bellozanne Sewerage Treatment Works (STW). δ15N isoplots maps indicate low diffusion of nitrogen out of St Aubin's Bay. St Mary's produced a varied δ15N isoplot map in comparison. δ15N was typically lower and is attributed to a smaller population and inefficient STW. Outflow of sewage/effluent at Morning Point, Hugh Town and Old Town produced elevated δ15N values in comparison to the island average. St Mary's inefficient sewerage treatment and reliance on septic tanks/soakaways complicates δ15N interpretation although it still indicates that nitrogen pollution is an island-wide issue. Future sewerage development and upgrades on islands are required to prevent similar effluent environmental issues as recorded in St Aubin's Bay. This study advocates the use of macroalgae as a bioindicator of nitrogen effluent in the marine environment.

The use of Chinese herbal medicine to improve quality of life in women undergoing chemotherapy for ovarian cancer: a double-blind placebo-controlled randomized trial with immunological monitoring.

BACKGROUND: This study aimed to evaluate traditional Chinese medicine (TCM) in improving quality of life (QOL), reducing chemotoxicity and modulating immune function in patients undergoing chemotherapy. PATIENTS AND METHODS: Patients with ovarian cancer were randomized to receive either TCM or placebo in addition to standard chemotherapy. The primary outcome was global health status (GHS) score, assessed by European Organization for Research and Treatment of Cancer questionnaire, while the secondary outcomes were other QOL items, chemotoxicity according to World Health Organization criteria and alterations in immune function as measured by immune cells count and the numbers of cytokines-secreting cells. RESULTS: There was no significant difference in the GHS between the two groups. With adjustment for stage, chemotherapy type, disease status, age and baseline value, emotional function, cognitive function and nausea and vomiting were found to be worse or less improved in the TCM group compared with placebo group after six cycles of chemotherapy. The TCM group had less neutropenia after three cycles (0% grade 4 neutropenia versus 28.6%). There were no other significant differences in terms of chemotoxicity. Lymphocyte counts and cytokine activities decreased less in the TCM group. CONCLUSIONS: TCM did not improve QOL but did have some effects in terms of maintaining immune function.

Efficacy upon 12-weeks after achievement of maximal dose and tolerability of lacosamide as an adjunctive therapy in epilepsy: Real world clinical experience.

Lacosamide (LCM) is a new generation antiepileptic drug. It has only been available in Asia in recent years. A retrospective study at two hospitals in Hong Kong was performed to investigate the post-marketing efficacy and tolerability of the drug. A total of 81 subjects were recruited, among which 88% had drug-resistant epilepsy. The most common type of epilepsy was focal with unknown etiology. All patients used LCM as adjunctive therapy. The 50% responder rate was 42% at 12 weeks after achievement of maximal dose of LCM. No specific factor correlated with responsiveness including concomitant enzyme-inducing or sodium channel blocking anticonvulsants. Withdrawal rate within first 12 weeks after drug initiation was 14% while that at any time upon follow-up was 23%. Two cases of uncommon adverse reaction of myoclonus were also reported. The mechanism was postulated to be the sodium channel inhibiting action of LCM. Our study has shown LCM to have comparable efficacy and tolerability in post-marketing experience when compared with the landmark randomized controlled trials.

Primary hepatic peripheral T-cell lymphoma in a patient with chronic hepatitis B infection.

We report a case of primary hepatic peripheral T-cell lymphoma in a patient with hepatitis B virus-related cirrhosis. This patient presented with a solitary hepatic lesion with computed tomography and magnetic resonance imaging features that did not resemble hepatocellular carcinoma. Subsequent biopsy of the lesion revealed that it was a peripheral T-cell lymphoma. The patient was successfully treated with multi-agent chemotherapy followed by radiofrequency ablation. Although hepatocellular carcinoma is the most frequently encountered primary hepatic tumour in patients with hepatitis B virus-related cirrhosis, primary hepatic lymphoma should also be borne in mind. Nevertheless, primary hepatic lymphoma is a rare entity, and has no proven association with chronic hepatitis B infection.

Measurement agreement between a newly developed sensing insole and traditional laboratory-based method for footstrike pattern detection in runners.

This study introduced a novel but simple method to continuously measure footstrike patterns in runners using inexpensive force sensors. Two force sensing resistors were firmly affixed at the heel and second toe of both insoles to collect the time signal of foot contact. A total of 109 healthy young adults (42 males and 67 females) were recruited in this study. They ran on an instrumented treadmill at 0°, +10°, and -10° inclinations and attempted rearfoot, midfoot, and forefoot landings using real time visual biofeedback. Intra-step strike index and onset time difference between two force sensors were measured and analyzed with univariate linear regression. We analyzed 25,655 footfalls and found that onset time difference between two sensors explained 80-84% of variation in the prediction model of strike index (R-squared = 0.799-0.836, p<0.001). However, the time windows to detect footstrike patterns on different surface inclinations were not consistent. These findings may allow laboratory-based gait retraining to be implemented in natural running environments to aid in both injury prevention and performance enhancement.

Polarity in Cell-Fate Acquisition in the Early Mouse Embryo.

Establishing polarity is a fundamental part of embryogenesis and can be traced back to the earliest developmental stages. It can be achieved in one of two ways: through the preexisting polarization of germ cells before fertilization or via symmetry breaking after fertilization. In mammals, it seems to be the latter, and we will discuss the various cytological and molecular events that lead up to this event, its mechanisms and the consequences. In mammals, the first polarization event occurs in the preimplantation period, when the embryo is but a cluster of cells, free-floating in the oviduct. This provides a unique, autonomous system to study the de novo polarization that is essential to life. In this review, we will cover modern and past studies on the polarization of the early embryo, using the mouse as a model system, as well as hypothesizing the potential implications and functions of the biological events involved.

Low-income pre-schoolers with higher temperamental surgency enjoy and respond more to food, mediating the path to higher body mass index.

BACKGROUND: Temperament is associated with obesity risk. However, the mechanisms linking temperament and eating behaviour to childhood adiposity are unclear. OBJECTIVES: To examine whether three temperament dimensions (surgency, effortful control and negative lability) are uniquely associated with an increased BMI z score (BMIz) concurrently and an excessive rate of change in BMIz longitudinally through four eating behaviours (food responsiveness, enjoyment of food, emotional overeating and satiety responsiveness) among low-income pre-schoolers, independent of home environment quality. METHODS: 379 pre-schoolers were recruited from Head Start in the Midwest region of the United States. Primary caregivers reported child temperament, eating behaviours and the level of chaos at home. Child BMIz was derived from weight and height measurements at ages 4, 5 and 6 years on average. RESULTS: Path analyses revealed that higher levels of surgency predicted more food responsiveness and enjoyment of food, which was in turn associated with higher concurrent BMIz, independent of effortful control, negative lability and home chaos. CONCLUSION: Low-income surgent pre-schoolers were more likely to have elevated BMIz as they were more inclined to eat in response to external cues and have a high appetitive drive. Obesity prevention programmes might target low-income children with surgent temperaments, and the identified eating behaviours.

Mycophenolate mofetil in the treatment of steroid-resistant primary focal segmental glomerulosclerosis.

We report our experience in using mycophenolate mofetil (MMF) for the treatment of steroid-resistant focal segmental glomerulosclerosis (FSGS) in two patients. Patient 1, who was treated on disease presentation, responded well with sustained complete remission. Patient 2, who had unsuccessful steroid treatment 4 yrs before and was re-treated with MMF, showed transient retardation in renal disease progression but eventually progressed to end-stage renal failure. Our observation illustrates that MMF could be useful in treating steroid-resistant FSGS if administered at an early phase of the disease, well before histologic damage becomes irreversible. Its efficacy requires validation in randomized, controlled trials. The current armamentaria for the treatment of this condition are also discussed.

The antibody response to a single antigenic determinant of the tobacco mosaic virus protein: analysis using monoclonal antibodies, mutant proteins and synthetic peptides.

Three hybridomas were selected which secreted monoclonal antibodies specific to a decapeptide determinant representing residues 103-112 of the tobacco mosaic virus protein ( TMVP ). A series of proteins from several strains of TMV which differ in the amino acid sequence in this region of the protein were used as probes for specificity analysis. The fine-specificity analysis was extended by assessing the binding of the antibodies with a panel of synthetic peptide analogues of the native decapeptide with amino acid substitutions at different locations. The binding of each synthetic peptide with each of the monoclonal antibodies was determined by the ability of the radiolabeled peptide to bind with the antibody. The binding of the decapeptide with antibodies was determined by equilibrium dialysis; the relative binding affinity of each peptide of the panel was determined by the capacity of the peptide to inhibit the binding between the antibody and the radiolabeled native decapeptide. The results demonstrated that a panel of synthetic peptide analogues constitutes a powerful tool for discerning the fine specificity of antibodies directed to a given determinant of a protein antigen. The data indicated that, although all of the antibodies recognized the same nominal decapeptide determinant, their binding with the different mutant proteins or with the synthetic peptides of the panel differed greatly, indicating dramatic differences in their fine specificity. The existence of such differences should be taken into consideration when assessing residues of a protein antigen that are involved in antibody binding. The differences which were found in monoclonal antibodies produced following immunization with the whole TMVP reflect differences which occur in heterogeneous serum antibody populations and point out the complexity of antigenic recognition even of as small an epitope as a decapeptide.

Synthetic peptides of envelope proteins of two different strains of simian AIDS retrovirus (SRV-1 and SRV-2) represent unique antigenic determinants for serum neutralizing antibodies.

There are at least three distinct serotypes of simian type D retrovirus (SRV) which exhibit extensive serological cross-reactivity, but no cross-reactivity exists at the level of serum neutralizing antibodies. Amino acid sequence analysis and hydrophobicity plots of SRV-1 and SRV-2 envelope proteins were compared in order to identify unique potential antigenic determinants to which respective neutralizing antibodies may be directed. Peptides representing residues 147-162 of SRV-1 and 96-102 of SRV-2 were synthesized and assessed for their immunoreactivity. Free peptide inhibition of strain-specific serum (rhesus) neutralizing antibodies to SRV-1 and SRV-2 was demonstrated using the SRV-1 147-162 peptide and the SRV-2 peptide, 96-102, respectively. Inhibition of serum neutralizing activity by these peptides was also strain-specific, showing no cross-inhibition. SRV-1 147-162 conjugated to a protein carrier and cross-linked to Sepharose beads specifically adsorbed neutralizing antibodies from SRV-1 immune rhesus sera. The antibodies eluted from the immunoadsorbent possessed SRV-1 neutralizing activity, but showed no effect on the infectivity of SRV-2. Peptide SRV-1 147-162 also exhibited the capacity to bind specifically with a mouse monoclonal antibody which neutralizes the infectivity of SRV-1. Mice immunized with a recombinant SRV-1 envelope protein or with whole, inactivated SRV-1 produced antibodies which bound the SRV-1 147-162 conjugate, but not the protein carrier itself. Mouse antibodies to the SRV-1 147-162 conjugate exhibited specific binding with both native SRV-1 and with recombinant SRV-1 envelope protein. These findings provide strong evidence that SRV-1 147-162 and SRV-2 96-102 constitute at least two unique antigenic determinants, or parts thereof, which participate in the strain-specific neutralizing antibody response. Moreover, the findings indicate that the SRV-1 neutralizing antibodies produced by monkeys and at least a certain population of neutralizing antibodies produced by mice recognize the same epitope of SRV-1.

Immunobiological properties of a recombinant simian retrovirus-1 envelope protein and a neutralizing monoclonal antibody directed against it.

We previously reported that an area encompassing amino acids 147-162 of the envelope region of the simian (type D) retrovirus serotype 1 (SRV-1) constitutes an antigenic site for the binding of murine and rhesus neutralizing antibodies. Neutralizing antibodies to SRV-2 are directed to a different area, encompassing residues 96-102 of SRV-2. This paper presents data on the activity of an SRV-1 recombinant envelope protein (rEP) and of monoclonal hybridoma cell line, C11B8, produced from murine spleen cells immunized with SRV-1 rEP. Purified monoclonal antibodies from C11B8 bind to the SRV-1 rEP and to both SRV-1 and SRV-2. However, the monoclonal antibody exhibits strain specificity in the capacity to neutralize SRV-1 infection in vitro. Thus, C11B8 neutralizes SRV-1 infection but fails to neutralize four other known serotypes of the virus. C11B8 also binds to an SRV-1 synthetic peptide representing residues 142-167, which encompasses the previously defined antigenic site of recognition for neutralizing antibodies to SRV-1. This paper also contains evidence that the SRV-1 rEP construct binds the site for SRV-1 attachment to the cell receptor. This is indicated by the ability of SRV-1 rEP to compete with SRV-1 (but not with SRV-2) and inhibit its infectivity in vitro. In addition, SRV-1 rEP inhibits the neutralizing activity of C11B8 against SRV-1 infection in vitro. SRV-1 rEP has no inhibitory effect on rhesus neutralizing antibodies to SRV-2. Taken together, the above findings indicate that immunity conferred at the level of neutralizing antibodies during SRV infection is strain-specific and involves the recognition of envelope sequences unique to each strain.

Reconstructing weighted networks from dynamics.

We present a method that reconstructs both the links and their relative coupling strength of bidirectional weighted networks. Our method requires only measurements of node dynamics as input. Using several examples, we demonstrate that our method can give accurate results for weighted random and weighted scale-free networks with both linear and nonlinear dynamics.

Acupuncture analgesia in rabbits.

The aim of this study was to verify the validity and reliability of analgesia elicited by acupuncture stimulation in rabbits. Ninety-five experiments were performed using 21 adult animals. The reaction time of the avoidance response elicited by noxious heat stimulation on the snout, and the presence or absence of the start response elicited by pin-prick and clamping of the skin were studied. Bilateral electric acupuncture stimulation in the area of Tsu-san-li and Shang-chu-hsu points in the hind legs was used. The animals were either held in a soft bag, loosely attached by cords, or suspended in a hammock; the eyes were either free of blindfolded. On the basis of operational behavioral measurements, it was found that acupuncture stimulation did not produce analgesia in undisturbed, placid animals. However, during agitated or fighting periods and the immobility reflex-like state, sometimes associated with acupuncture maneuvers, long reaction times were observed. Pin-pricking and clamping stimulation of the skin were not reliable methods of noxious stimulation in the rabbit.

Localisation of CD10 to biliary canaliculi by immunoelectron microscopical examination.

Common acute lymphoblastic leukaemia antigen (CALLA) was first characterised in lymphoid leukaemic cells. The antigen is present in different stages of lymphoid cell differentiation as well as in subsets of myeloid cells, and further studies have also shown its presence in non-lymphoid tissues. The recent cloning and sequencing of the gene permitted deduction of its amino acid sequence which is identical with the human membrane-associated enzyme, neutral endopeptidase. Strong immunostaining for CALLA was detected in the human liver with a canalicular pattern. Immunoelectron microscopy also confirmed that the antigen was localised only in the area of the bile canaliculi. Although the function of neutral endopeptidase in the canaliculi is unknown, this antigen may prove useful in the study of biliary function and diseases.

Hepatic myospherulosis complicating portal vein embolisation.

AIMS: Myospherulosis is a rare condition characterised by sac-like structures containing spheroid bodies in cysts or cystic spaces in the tissue. This condition has not previously been reported in the liver. The association with previous portal vein embolisation using a mixture of butyl 2-cyanoacrylate and ethiodised oil and the proposed mechanism of pathogenesis are discussed. METHODS: Samples from 8 patients treated by hepatectomy after portal vein embolisation using a mixture of butyl 2-cyanoacrylate and ethiodised oil were retrieved from the archives of the United Christian Hospital, Hong Kong. The histological specimens were reviewed. A panel of histochemical and immunohistochemical stains was used. RESULTS: All cases showed hepatic myospherulosis within the veins. The veins were denuded of endothelium, which was replaced by granulation tissue and fibrous tissue with a lymphoplasmacytic infiltrate. Foreign body-type giant cells (six cases) and eosinophilic infiltrates (seven cases) were noted in most cases. Both parent bodies and endobodies were stained red by Papanicolaou and Masson's trichrome and stained blue by solochrome cyanine. The endobodies showed immunoreactivity towards glycophorin A. They were negative for Alcian blue, periodic acid Schiff, Grocott, and Ziehl-Neelsen stains. CONCLUSIONS: The endobodies of myospherulosis may be misdiagnosed as fungi or algae by the unwary. The clinical history, intravascular location, lack of staining with periodic acid Schiff and Grocott stains, and positive glycophorin A staining are generally sufficient for a confident diagnosis of myospherulosis.

Chondrosarcoma metastatic to the heart.

This review summarizes the clinical manifestations and results of treatment of chondrosarcoma metastatic to the heart. Including the patient in the present report, a total of 18 patients have been reported. The most common site of cardiac metastasis was the right atrium. Dyspnea and pleuritic chest pain were the most common symptoms associated with cardiac metastases. The median time from the initial diagnosis of primary chondrosarcoma to death was 36 months, and the median time from the initiation of cardiac symptoms to death was 2 months. Treatment of primary chondrosarcoma included local radical resection in 14 patients. Treatment of cardiac metastases consisted of palliative support in 13 patients and surgical resection in 5 patients. Median survival following the development of cardiac symptoms was 2 months for patients treated nonsurgically and 18 months for those who underwent resection of cardiac metastases. The longest survival (24 and 28 months) was obtained in 2 patients with metastases confined to the heart that were successfully resected soon after development of cardiac symptoms. These results suggest that surgical resection of cardiac metastases in patients without widespread other metastases can result in substantial prolongation of life.

Malignant lymphoma masquerading as multiple myeloma.

A case of non-Hodgkin's lymphoma with features mimicking that of multiple myeloma is reported. A 67-year-old man presented with lymphadenopathy and the classic constellation of symptoms and signs of multiple myeloma, including generalised bone pain, hypercalcemia and multiple osteolytic lesions on the skeletal survey. However, cervical lymph node biopsy showed diffuse large cell lymphoma and marrow aspirate showed infiltration with lymphoma cells different in both morphology and surface markers to myeloma cells.